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CLINICAL REVIEW

Cleft lip and/or palate and breathing during sleep
Joanna E. MacLean a,b,*, Peter Hayward c, Dominic A. Fitzgerald a,b, Karen Waters a,b
a Discipline of Paediatrics & Child Health, Faculty of Medicine, University of Sydney, NSW, Australia
b Department of Respiratory Medicine, The Children’s Hospital at Westmead, Sydney, NSW, Australia
c Department of Plastic Surgery, The Children’s Hospital at Westmead, Sydney, NSW, Australia

Keywords:

Sleep apnoea
Palatoplasty
Pharyngoplasty
Pharyngeal flap
Velo-pharyngeal insufficiency
Prone positioning
Adenotonsillectomy
Continuous positive airway pressure
Mandibular distraction

Conclusion

Dysfunction of the palatal muscles controlling the soft palate in conjunction with structural abnormalities of the maxilla and
mandible producing a small nasopharyngeal airway underlie the high risk for SDB in children with CL/P. The risk is compounded by surgical procedures to correct the structural abnormalities which further reduce airway dimensions. Until further information about specific risk factors is obtained, children with a CL/P, regardless of surgical status, should be screened for SDB. Treatment options need to be balanced against risks, particularly deterioration in speech function after adenoidectomy, or persisting SDB because of the abnormal function and anatomy of their palate and airway.
Further research into the short- and long-term outcomes of SDB in CL/P is required to enable clinicians to make appropriate treatment decisions for children with CL/P.


Practice points

Children with CL/P should be screened for symptoms of
SDB.
A low threshold should be set for completing PSG for
the investigation of SDB in children with CL/P.
While standard therapy for SDB may be appropriate for
children with CL/P, the decision to remove adenoid
tissue should be done in consultation with those experienced in the care of children with CL/P.
Follow-up of children with CL/P is required after treatment to determine the success of surgical procedures
and to identify residual SDB.


Research agenda
Prospective longitudinal studies of infants and children
with CL/P are needed to determine the risk, important
risk factors and outcome for SDB associated with CL/P.
Treatment studies of children with SDB should include
children with a history of CL/P to determine the relative
contribution of facial structure to the success of treatment modalities for SDB.


s u m m a r y

Cleft of the lip and/or palate (CL/P) is a common defect which is associated with changes in facial
structures and a smaller upper airway. As a result, infants and children with CL/P have an increased risk
of sleep disordered breathing (SDB). This paper will review the anatomical and functional factors which
place infants and children with CL/P at increased risk of SDB as well as review the literature which
defines the magnitude of this risk. The information available on treatment of SDB in infants and children
with CL/P will be presented. Finally, outstanding issues relevant to SDB in children with CL/P are discussed with direction for future research.

2009 Elsevier Ltd. All rights reserved.

Introduction

Cleft of the lip and/or palate (CL/P) is a common birth defect. The
defect results from disruption to the development of the facial and
airway structures. This results in abnormalities in the final
conformation and function of the upper airway. The majority of
clefts occur in isolation while the remainder of clefts occur with
other congenital anomalies or chromosomal abnormalities.
Together, the type of cleft and the associated malformations
influence the type of airway and respiratory related problems as
well as their clinical presentations.
This review summarizes what is currently known about CL/P as
it relates to breathing during sleep. The current literature does not
permit an accurate determination of the true risk of sleep disordered breathing (SDB) associated with cleft. Individual reports
reveal that infants with cleft palate may have life-threatening
airway obstruction, but they can also suffer from mild to severe
SDB. Cohort studies tend to be limited and to study specific subgroups such as those undergoing surgical procedures or else
include only short periods of follow-up. In this review, potential
risk factors, clinical presentations, and treatment options for SDB in
infants and children with CL/P have been considered including
clefts associated with Pierre Robin sequence. A number of issues
relating to the management of SDB in children with CL/P cannot be
answered from the existing literature and support the need for
future research.

Overview of cleft lip and/or palate

CL/P is a congenital malformation with an incidence of 0.69–
2.51 per 1000 births.1–4 Embryonic development of the primary (lip
and alveolus) and secondary (hard and soft) palates occur between
the 6th and 9th week of human development. CL/P results from
failure of the medial nasal process to contact or to maintain contact
with the lateral nasal and maxillary processes and, therefore,
constitute a disruption of normal development.5 This disrupted
growth results in a spectrum of abnormalities from cleft lip to
bilateral complete cleft lip and palate.
While the exact mechanisms accounting for CL/P are not well
understood, genetic and environmental factors appear to influence
the severity of this malformation. The abnormality can be described
in terms of the effects on anatomical structures in the transverse
plane, the sagittal plane and the tissue level that is affected.6,7 Cleft
classification systems denote both the anatomical structures and
tissue level involved in the cleft.8 A submucous cleft affects the
same anatomical structures and tissue levels but is covered with
soft tissue so the cleft is less visible.
The EUROCAT epidemiological study of CL/P showed that 70.8%
of clefts occur as isolated malformations while 29.2% occur with
other malformations, chromosomal aberrations or syndromes.4 The
most common associated malformations affect the musculoskeletal, central nervous and cardiac systems.4,9 The occurrence of
associated malformations does not necessarily correlate with the
severity of the cleft defect.10 Both the type of cleft and the
associated malformations can predispose children with CL/P to
upper airway obstruction.
Common co-morbidities associated with CL/P, in addition to
airway obstruction, include feeding difficulties, growth failure,
speech abnormalities, and developmental delay. Feeding difficulties
are more common in newborns and children with syndromes and
may persist beyond the first year of life.11,12 Failure to thrive is more
common in infants with cleft palate compared to those with cleft lip
alone and in infants with CL/P in the context of syndromes
compared to those without syndromes.12 Growth concerns may
persist into childhood, but catch up growth is often seen after
surgical repair of the cleft.13–15 Infants and children with CL/P show
characteristic changes in pre-speech and speech with these difficulties persisting into adolescence.16–18 Children with cleft palate
are also at increased risk of delayed development with a decline in
mental development noted over the first 2 years of life.19,20 Children
with cleft lip and palate or Pierre Robin sequence show greater
cognitive impairment than children with cleft lip alone while children with associated malformations show lower average developmental scores than children without associated malformations.20,21
Children with Pierre Robin sequence are often studied as
a distinct group. The sequence includes a small, retruded mandible
and glossoptosis.22 It is associated with a U-shaped cleft of the soft
palate with possible extension of the defect into the hard palate.
While the majority of cases of Pierre Robin sequence occur in
isolation, 20–40% occur in the context of another syndrome such as
Stickler syndrome or velo-cardio-facial syndrome.23–25 Feeding
difficulties and failure to thrive are also common in this group of
children.23,25
Surgical management is the mainstay of CL/P management
including repair of cleft lip, palate closure, management of velopharyngeal insufficiency, and orthognathic surgery. Cleft lip repair
involves repairing the defect in both the lip and alveolus and is
generally repaired between 3 and 6 months of age. Palatoplasty is
the main technique used for closure or reconstruction of the hard
and soft palates. The timing and type of palate repair varies by type
of cleft and other associated anomalies as well as by surgeon. Palate
repair is generally undertaken between 6 and 14 months but may be
delayed by up to 4 years. The timing of hard palate repair is reported
to influence speech outcomes with early repair favouring improved
speech.26 On the other hand, delayed repair favours mid-facial
growth27 although a recent systematic review of the effect of timing
of hard palate repair on mid-facial growth was inconclusive.28
Velo-pharyngeal insufficiency, or incomplete closure of the
velo-pharyngeal port during speech, is seen in 25% of children with
cleft.29 Pharyngoplasty and pharyngeal flap surgery are two
common procedures used to correct velo-pharyngeal insufficiency.
In order to improve speech intelligibility, nasal resonance is
decreased by limiting the airflow through the nose by reducing the
space between the soft palate and the posterior pharyngeal wall.
Approximately 10–35% of children with CL/P require surgery for
velo-pharngeal insufficiency.30–32 Improvement in velo-pharyngeal
insufficiency, and hence speech, is related to the reduction in nasal
airflow with the greatest improvement in speech associated with
the lowest amount of nasal airflow. Children with cleft may also
require additional orthognathic surgery for correction of dental
misalignment as well as retrognathic facial deformity at the end of
the growth period.33–35

* Corresponding author at: Department of Respiratory Medicine, The Children’s
Hospital at Westmead, Locked Bag 4001, Westmead, NSW, Australia. Tel.: þ61 2
9845 0000; fax: þ61 2 9845 3633.
E-mail address: JoannaM4@med.usyd.edu.au (J.E. MacLean).
Contents lists available at ScienceDirect
Sleep Medicine Reviews
journal homepage: http://www.elsevier.com/locate/smrv
1087-0792/$ – see front matter 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.smrv.2009.03.001
Sleep Medicine Reviews 13 (2009) 345–354


Predisposition to SDB

Surgical procedures that result in narrowing of the posterior
airway space are the most readily identified risk factor for SDB
associated with cleft. However, both anatomical and functional
changes associated with CL/P increase the risk of SDB, particularly
obstructive sleep apnoea (OSA). Kadowaki and colleagues36
reported that 40% of newborn mice with cleft lip and palate had
cyanosis, which they concluded was related to airway obstruction.
The mice with cyanosis had more severe cleft abnormalities
(bilateral complete cleft lip and palate) and unelevated palatal
shelves compared to the acyanotic group.
Changes in human facial morphology associated with cleft result
in a small midface and a retruded mandible. This results from
decreased posterior length and height of the maxilla, increased
width of the maxilla, basal maxillary retrognathia, increased width
of the nasal cavity, decreased length of the mandible, and
mandibular retrognathia which result in reduced size of the
pharyngeal airway.37 Clefts of the secondary (hard and soft) palate
but not the primary (lip and alveolus) palate result in smaller
maximal palatal height while palatal depth is decreased in all cleft
types except submucous cleft.38 All maxillary dimensions are
smaller in individuals with a history of cleft, resulting in mid-face
hypoplasia compared to individuals without cleft. Missing teeth
affect palatal dimensions, especially palatal height. Palatal height is
greater in males with cleft compared to females with cleft, whereas
non-cleft males also show greater palatal width and depth than
non-cleft females.
Upper airway dimensions are reduced with CL/P even after
surgical correction of the defect. Comparing cephalometric
measurements between children with a history of cleft palate
repair and healthy controls, Rose and colleagues39 found that
children with cleft had smaller pharyngeal airway size with a retrognathic position of the maxilla. Pharyngeal width at the maxillary
plane and the narrowest point of the pharynx were decreased with
an inferiorly positioned hyoid. No difference was seen in tonsil or
adenoid dimensions between the two groups. Posterior airway
space is also narrowed in children with cleft compared to controls.
In one study, 60% of children with cleft showed narrowing of at
least one dimension of the posterior airway space compared to 7%
of controls.40 In a group of 5-year-old boys with unilateral cleft lip
and palate, there was shortening of the anterior cranial base in the
region of the middle cranial fossa and reduced height of the
sphenoid body with a normal cranial base angle compared to
controls.41
Nasal airway dimensions are affected by cleft lip but not cleft
palate. Adults with bilateral cleft lip and palate have greater
impairment of nasal airway calibre compared to those with
unilateral cleft lip and palate or with cleft palate alone.42 Acoustic
rhinometry demonstrated pathological nostril obstruction on the
cleft side in 75% of adults with a history of unilateral cleft lip and
palate compared to 15% on the non-cleft side43,44 with some
patients showing multiple sites of obstruction.44 The cleft side also
showed greater response to decongestive agents suggesting that
mucosal hypertrophy likely contributes to nasal airway obstruction.45 While nasal calibre and airflow are affected by clefting,
olfactory function is maintained.46
Oropharyngeal musculature is also disrupted by a cleft of the
secondary (hard and soft) palate resulting in abnormal airway
function in addition to structural changes. Velo-pharyngeal function in children with cleft has been shown to differ from children
without cleft in studies of speech and swallowing.47–50 While there
are no studies examining the role of palatal muscle function in
airway patency in association with cleft palate, studies in adult
humans support the important role of palatal muscles in maintaining airway patency.51–53
The changes in craniofacial dimensions associated with a history
of cleft persist beyond the period of skeletal growth. In a study of
craniofacial dimensions adults with a history of bilateral cleft lip
and palate, compared to control adults, had smaller mandibular
dimensions, larger vertical craniofacial dimensions, larger craniocervical angulation, smaller depth of oropharynx and an inferiorly
positioned hyoid.54 However, adults with a history of bilateral cleft
lip and palate, compared to adults with OSA, showed no difference
in mandibular sagittal dimensions, vertical craniofacial dimensions,
craniocervical angulation, pharyngeal dimensions or vertical hyoid
position. Adults with a history of bilateral cleft lip and palate
showed a retruded maxilla compared to both the OSA and the
control groups.

Nomenclature

AHI apnoea–hypopnea index
BiPAP bi-level positive airway pressure
CL/P cleft lip and/or palate
CPAP continuous positive airway pressure
DI desaturation index
LSAT lowest oxygen saturation during sleep
OAHI total obstructive apnoeas and hypopneas per hour
of sleep
nCPAP Nasal-continuous positive airway pressure
OSA obstructive sleep apnoea
PSG polysomnography
RDI respiratory disturbance index
SDB sleep disordered breathing
VPI velo-pharyngeal insufficiency
346 J.E. MacLean et al. / Sleep Medicine Reviews 13 (2009) 345–354

CL/P and SDB

The literature was searched for relevant original research, case
series and case reports using Ovid MEDLINE (1950–2009). The
results of searches using the terms ‘cleft lip’ and ‘cleft palate’ were
combined with the results of searches using the terms ‘sleep
apnoea syndrome’, ‘apnoea’ and ‘airway obstruction’. The resulting
list of articles, with abstracts where available, was reviewed for
relevance to this review. The full texts of all relevant journal articles
were reviewed for report on SDB or OSA and CL/P. Thirty journal
articles that describe SDB or OSA as a primary or secondary
outcome in the context of CL/P were identified. Three studies
reviewed SDB across populations of children with CL/P55–57 with 6
studies reporting on the epidemiology of SDB in infants with Pierre
Robin sequence.23–25,58–60 The remainder of studies investigated
the relationship between surgical procedures and SDB or OSA.
The criteria used to define SDB or OSA in these studies vary and
are often not consistent with current standards. We used the
original article to report polysomnography (PSG) results including:
apnoea–hypopnea index (AHI; total number of apnoeas and
hypopnoeas per hour of sleep), respiratory disturbance index (RDI;
total number respiratory events per hour of sleep), obstructive AHI
(OAHI; total number of obstructive apnoeas and hypopneas per
hour of sleep), desaturation index (DI; total number of desaturation
events per hours of sleep) and lowest oxygen saturation
during sleep (LSAT). Where available, we also included the definition of terms as used by the authors. Where possible, we also
presented raw data or PSG results to allow comparison between
studies.

Prevalence of SDB

Three studies support an increased incidence of SDB amongst
children with CL/P. This includes two retrospective reviews of SDB
from cleft clinics in tertiary care centres and a questionnaire study
of pre-school children with CL/P. All three studies include children
at different ages and therefore different stages of CL/P care who
may, or may not have undergone surgery.
Muntz and colleagues55 retrospectively reviewed all children
presenting to a tertiary cleft and craniofacial team over three years
and, using clinical records, found symptoms of SDB in 22% of 539
children. More children with syndromes had symptoms of SDB
compared to those without syndromes (34% vs 17%). Sixty-nine
children underwent PSG, 70% of whom had an identified syndrome.
All but 1 PSG was abnormal (AHI > 1 event/h). Eighty-eight percent
of studies showed OSA (OAHI > 1 event/h) and 23% showed severe
OSA (OAHI > 10 events/h).
A second retrospective review examined PSG data from children
with CL/P over a 15 year period at one institution.56 A total of 99
PSGs were available from 62 children. Sixty-seven percent of those
who underwent PSG had an identified syndrome or other anomalies. Twenty-four percent of children were less than 9 months
old when the first PSG was completed. Baseline sleep studies
identified SDB in 87% of children (respiratory disturbance
index; RDI > 1 event/h) with 28% of children showing severe SDB
(RDI > 10 events/h). Young age and pre-surgical (pre-palate
closure) status were both associated with more severe OSA on univariate analysis, but only pre-surgical status remained significant
on multi-variate analysis.
The only study to investigate the overall incidence of SDB in
children with CL/P used questionnaires to examine symptoms of
SDB in pre-school children.57 All children less than 5 years from
a single tertiary cleft clinic were eligible for screening and
completed questionnaires were returned from 72% of 342 children,
14% of whom had cleft in the context of a syndrome. Snoring was
reported in 25% of children with witnessed apnoea reported in 4%.
Questionnaire scores indicated a likely diagnosis of OSA in 31.4% of
children. Only 29% of those children with OSA on questionnaire had
undergone investigation for those symptoms. The only clinical
factor associated with OSA on questionnaire was the identification
of a syndrome.
Six studies examining the incidence of SDB in Pierre Robin
sequence were identified. This included a series of 110 consecutive
patients with Pierre Robin sequence where 25% presented for
medical care because of severe breathing problems in the newborn
period.24 Spier and colleagues59 described snoring in 13 of 20 (65%)
patients with Pierre Robin sequence, only 7 of whom underwent
PSG. Compared to normal subjects, children with Pierre Robin
sequence had higher AHI, lower mean and minimum oxygen
saturation values and more disturbed sleep. One subject who had
undergone mandibular corrective surgery for presumed OSA had
no obstructive events post-operatively but had 82 central apnoea
events/h. The snoring observed in this patient was found to be due
to the large inspiratory efforts that terminated central apnoeas.
Another study of 13 infants monitored with 4 channel recordings
(electrocardiogram, respiratory motion detection, airflow and
oxygen saturation) found that 46% of these infants had significant
airway obstruction in the prone position.60 A retrospective review
of 11 patients with Pierre Robin sequence over five years identified
upper airway obstruction in 10 infants (91%) with delayed
presentation (average 36.6 days) of airway obstruction in 7
infants.58 Recent studies also attribute the increased mortality
(3–4%) in infants and children with Pierre Robin sequence group to
OSA.23,25
Together these studies support an increased risk for SDB in
infants and children with CL/P. The estimated risk of SDB in children
with CL/P is between 22 and 65%24,55–59 while up to 28% of these
are likely to have severe SDB.55,56 The prevalence of SDB is greater
in the subgroup of infants and children with syndromes as well as
those with Pierre Robin sequence. Further work is needed to define
specific risk factors for SDB amongst children with CL/P.

J.E. MacLean et al. / Sleep Medicine Reviews 13 (2009) 345–354 347

Risk of SDB and surgical procedures

Cleft lip repair
Cleft lip repair is rarely associated with airway compromise.
Josephson and colleagues61 reported OSA following cleft lip repair
in two neonates. Investigation for OSA was not undertaken in these
neonates prior to surgery. It is possible that surgery exacerbated
unidentified OSA or that it resulted in OSA because of increased
nasal obstruction.

Palatoplasty

Four studies have examined the occurrence of SDB in association
with primary palatoplasty (Table 1) across a wide age-range
(14 mo–22 yr).62–65 Two studies excluded children with
syndromes62,65 while a third included one child with Pierre Robin
sequence.64 None of the studies identified SDB pre-operatively
although one study reported snoring in 30% of children preoperatively. Only two studies excluded SDB pre-operatively by PSG
but all 4 studies reported post-operative PSG results.

Table 1

Summary of studies investigating SDB before and after palatoplasty in children with cleft palate. The definitions of AHI and RDI were identical for all studies: the number of
apnoeas and hyponoeas per hour of sleep time. All studies, except Orr et al.,63 defined OSA and SDB as an event rate (AHI or RDI) > 1 event/h. Orr et al.63 defined significant OSA
as >5 events/h.
Reference N Age at
surgery
Age/timing at
post-operative PSG
Procedures Pre-operative Post-operative
Diagnoses PSG outcome Diagnoses PSG outcomes
Orr et al.63 10 14–18 mo Post-operative
PSG at 2–3 d,
3 mos
von Langenbeck,
intervelar veloplasty
0% OSA RDI 1.51 0.78 0% OSA 2–3 d: RDI 2.26 3.60,
3 mos: RDI 0.50 0.59
Rose et al.64 43 13.0 4.1
mo
6.3–22.5 yr Modified Langenbeck,
Ernst, Veau, Axhausen
5% SDB RDI 2.44 1.29,
Apnoea indexb 0.23 0.21
DI 0.7 0.48,
LSAT 86.4 5.4
Liao et al.65 a 10 5.1 1.1 yr Furlow 30% snoring
0% OSA
RDI 0.4 0.4DI
0.3 0.2LSAT 94 4
1 wk: 100% snoring,
100% mild OSA;
1 wk: RDI 1.8 0.5,
DI 0.2 0.3, LSAT 91 7
3 mo: 40% snoring,
20% OSA;
3 mos: RDI 0.8 0.5,
DI 0.2 0.3, LSAT 91 3
Liao et al.62 a 20 6.1 2.3 yr Post-operative
PSG at 9.3 2.1
mo
Furlow No symptoms 35% snoring
post-operatively;
20% OSA
RDI 1.3 1.6, DI 0.4 0.2,
LSAT 91.1 4.5

AHI: apnoea-hypopnoea index, d: days, DI: desaturation index, LSAT: lowest oxygen saturation during sleep, mo: months, OSA: obstructive sleep apnoea, PSG: polysomnography, RDI: respiratory disturbance index, wk: week, yr: years.
a Palatoplasty was performed for velo-pharyngeal insufficiency.
b Defined by authors as number of obstructive and mixed apnoeas of at least two respiratory cycles’ duration per hour of sleep time.

Table 2

Summary of studies investigating SDB before and after pharyngeal flap in children and adults with cleft palate. The definition of AHI and RDI were identical for all studies: the
number of apnoeas and hyponoeas per hour of sleep time. Orr et al.63 and Sirois et al.68 defined SDB as an event rate (AHI or RDI) >5 events/h. Abramson et al.69 did not include
a definition of polysomnography index. Liao et al. 62,70 defined OSA as an RDI > 1 event/h.
Reference N Age at
surgery
Age/timing at
post-operative PSG
Pre-operative Post-operative
Diagnoses PSG outcomes Diagnoses PSG outcomes
Orr et al.,63 10 4–9 yr Post-operative
PSG at 2–3 d, 3 mo
0% SDB RDI 1.39 1.58 2–3 d: 90% SDB;
3 mo: 20%
2–3 d: RDI 24.65 24.64,
3 mo: RDI 2.93 4.95
Sirois et al.,68 a 26 6.7 yr
(2–22 yr)
1–15 d post-operative No symptoms
of SDB
AHI 2.54 2.12 42% SDB AHI 19.75 17.51
Abramson et al.,69 b 7 >5 yr 86% OSA clinically Polysomnographyc index >28
(range 28–62) for 6 of 7
Liao et al.,70 28 6.3 2.3 yr 11.3 mo (6.0–13.5 mo) No symptoms
of OSA
93% OSA in children Children Adults
10 28 9.7 yr 9.6 mo (6.1–14.2 mo) 90% OSA in adults OAHI <1 in 2,
LSAT 87 8
OAHI <5 in 1,
LSAT 90
OAHI 1–5 in 11,
LSAT 89 3
OAHI 5–20 in 8,
LSAT 90 2
OAHI >5 in 15,
LSAT 85 5
OAHI >20 in 1,
LSAT 87
Liao et al.,62 28 6.4 2.3 yr No symptoms
of SDB
96% developed snoring;
96% OSA
RDI 7.3 6.7,
DI 1.9 2.4,
LSAT 86.2 3.8

AHI: apnoea-hypopnoea index, d: days, DI: desaturation index, LSAT: lowest oxygen saturation during sleep, mo: months, OSA: obstructive sleep apnoea, PSG: polysomnography, RDI: respiratory disturbance index, SDB: sleep disordered breathing, yr: years.
a 26/40 had cleft palate as underlying diagnosis associate with velo-pharyngeal insufficiency, reported results include only children with cleft. AHI is reported only for 11
subjects with sleep apnoea post-operatively (AHI > 5 events/h) on post-operatively PSG. Of these children, 6 had an obstructive pattern and 5 had a central pattern.
b Included only children with non-syndromic Robin sequence.
c Not defined.

348 J.E. MacLean et al. / Sleep Medicine Reviews 13 (2009) 345–354

The Post-operative RDIs ranged from 0.5 to 2.44 events/h with wide confidence intervals suggesting that the majority of children had mild
OSA. The post-operative incidence of SDB ranged from 0% to 100%
at 1 week falling to 40% at 3 months post-operatively.
Two additional studies report the incidence of airway obstruction following palatoplasty but did not include assessment for SDB
in all children.66,67 Antony and Sloan66 undertook a 10 year review
of 247 patients undergoing palatoplasty and reported postoperative airway problems in 14 children (6%). The mean age at
palatoplasty was 18 months (7–52 months). All but 1 of the
14 children had other anomalies and 7 had Pierre Robin sequence.
Lin and colleagues67 reviewed 24 children who had undergone
either a combined levator retropositioning and pharyngeal flap or
a double-opposing z-plasty for correction of cleft palate. Of this
group, 2 children (8%) developed severe post-operative OSA.
Together, these studies support a risk for SDB in children after
palatoplasty but the magnitude of the risk is unclear. Differences in
the age at surgery, surgical techniques and inclusion of children
with syndromes make it difficult to compare results between
studies. Estimates of the risk of SDB following palatoplasty range
from 6 to 40%.62–67 Importantly, little information is available about
the pre-operative risk for SDB.

Pharyngeal flap

Five studies reported SDB as a primary outcome in children with
cleft palate after pharyngeal flap surgery and reported postoperative PSG results (Table 2).62,63,68–70 One study included only
children with Robin sequence69 and one included all children
undergoing pharyngeal flap regardless of syndrome status.68
The timing of PSG following surgery varied from 5 days68 to
11 months70 with one study providing no information on the
timing of PSG relative to surgery.69 All studies reported that the
incidence of SDB or OSA increased post-operatively, affecting
42–96% of the patients studied.
Four studies included OSA as an outcome in retrospective
reviews of children undergoing pharyngeal flap surgery where PSG
was not undertaken in all children.71–74 In a 3-year review of 585
children, 18 children (3%) had symptoms of OSA and 15 (2.5%) had
confirmed OSA on PSG based on an apnoea index >5 events/h and
a mean decrease in arterial oxygen saturation greater than 10%
during apnoea epidoses.71 Although 87% of those with OSA after
pharyngeal flap had large tonsils, it is not clear what proportion of
the entire group had large tonsils. Flap width was not associated
with the degree of airway obstruction. Amongst 111 children who
underwent posterior pharyngeal flap surgery for velo-pharyngeal
insufficiency, the incidence of nocturnal respiratory obstruction
was reported as a late complication in 10.5% of patients with 75% of
these children having Pierre Robin sequence.72 A high risk of OSA in
children with Pierre Robin sequence after pharyngeal flap surgery
is supported by another study.75 Lesavoy and colleagues73 reported
a 38% incidence of perioperative airway obstruction in a series of 29
children undergoing pharyngeal flap for velo-pharyngeal insufficiency. Finally, a recent retrospective review of 222 consecutive
pharyngeal flap surgeries at a mean age of 6.4 years reported the
need for supplemental oxygen post-operatively in 12 patients
(8%).74 Not all patients underwent late evaluation, but only 5 children (3.3%) demonstrated OSA on follow-up at 6 months postoperatively.
There are several isolated case reports describing severe airway
obstruction and death following pharyngeal flap surgery. From
a series of three children undergoing pharyngeal flap for velopharyngeal insufficiency, one patient died after discharge from
hospital; the patient had velo-cardio-facial syndrome and a history
of repaired cleft palate.76 Severe airway obstruction during sleep
necessitated re-intubation two days after surgery with no report of
objective measurement of her breathing during sleep prior to
discharge. She died in her sleep four weeks following surgery. In
another case, an infant who underwent combined palatoplasty and
pharyngeal flap suffered cor pulmonale two years after surgery.77
Unrecognized OSA may well have contributed to the development
of pulmonary hypertension and cor pulmonale. While such severe
outcomes are devastating, they are rare and none of the case series
or systematic chart reviews report mortality associated with
pharyngeal flap surgery.

To summarize, pharyngeal flap surgery confers a risk of OSA
between 3 and 96%62,63,68–70,70–74 with retrospective studies suggesting a lower risk than prospective studies. Older studies support
a risk of severe airway obstruction and death following pharyngeal
flap surgery. Syndromes, including Pierre Robin sequence, and the
presence of large tonsils likely put children at higher risk.

Pharyngoplasty

Two studies examined SDB before and after pharyngoplasty
(Table 3).78,79 Abyholm and colleagues78 reported that 9.5% of
subjects had OSA pre-operatively compared to 15% one month after
surgery and 6.3% 12 months post-operatively. Sleep structure and
RDI were examined in a smaller study by Saint Raymond and
colleagues79 in 17 consecutive patients with a mean age of 14 8
years undergoing sphincter pharyngoplasty. The AHI, desaturation
index (DI) and lowest nocturnal oxygen saturation (LSAT) did not
differ between pre- and post-operative studies, but slow-wave
sleep was significantly reduced on follow-up studies at an average
of 164 days post-operatively.
One additional study examined 16 patients undergoing pharyngoplasty for velo-pharyngeal insufficiency and reported negative
results. In this study, although two patients had symptoms of OSA,
none were reported to have post-operative OSA. However, preoperative PSGs were not performed and the criteria to define OSA

Table 3

investigating SDB before and after pharyngoplasty in children and adults with cleft palate. The definition of AHI used by Saint Raymond et al.79 was the
number of apnoeas and hyponoeas per hour of sleep time with OSA defined by an AHI 3 events/h. Abyholm et al.78 defined the obstructive apnoea index (OAI) as the number
of episodes of the absence of airflow with continuing respiratory efforts per hour of sleep and OSA as an OAI > 1.0 events/h with a lowest oxygen saturation during sleep <93%.
Reference N Age at
surgery
Timing of
post-operative PSG
Pre-operative Post-operative
Diagnoses PSG outcomes Diagnoses PSG outcomes
Saint Raymond et al.79 17 14 8 yr 164 d (88 to 624 d) OSA 82% AHI 6.5 6.0 OSA 76% AHI 7.9 5.9
Apnoea index 0.7 0.5 Apnoea index 0.7 1.0
LSAT 91.6 3.5 LSAT 92.8 2.3
Abyholm et al.78 a 39 3–25 yr 1 mo, 12 mo OSA 9.5% OAI 0.19 0.53 1 mo: OSA 15% 1 mo: OAI 0.64 1.14, LSAT 94 4
LSAT 95 2 12 mo: OSA 6.3% 12 mo: OAI 0.19 0.42, LSAT 94 2
AHI: apnoea-hypopnoea index, d: days, LSAT: lowest oxygen saturation during sleep, mo: months, OSA: obstructive sleep apnoea, PSG: polysomnography, yr: years.
a Measurements of OAI and LSAT available for 21 subjects pre-operatively, 20 subjects at 1 mos and 16 subjects at 12 mos.

J.E. MacLean et al. / Sleep Medicine Reviews 13 (2009) 345–354 349

post-operatively was an RDI > 20 events/h, which constitutes
severe disease by current paediatric standards.80 Post-operative
OSA was not reported after the push-back operation for velopharyngeal insufficiency.81
Comparison of surgical procedures
Five studies compare OSA outcomes between different surgical
procedures used for palate closure or to treat velo-pharyngeal
insufficiency.62,63,67,78,80
One study compared OSA outcomes after different types of
primary repair of the palate. Lin and colleagues67 compared the
outcome of combined levator retropositioning and pharyngeal flap
to those after double-opposing z-plasty. Although sleep related
symptoms and investigations were not reported for the entire
group, 2 of 10 children with levator repositioning developed severe
OSA after surgery compared to none of the children who underwent double-opposing z-plasty.
Pharyngoplasty and pharyngeal flap are consistently reported to
confer a higher risk for OSA than palatoplasty. Orr and colleagues63
reported no OSA after von Langenbeck palatoplasty but a 40%
incidence of OSA at 3 months post-operatively in children undergoing superiorly based pharyngoplasty. Liao and colleagues62 also
reported a higher incidence of OSA in patients undergoing
a pharyngeal flap for velo-pharyngeal insufficiency compared to
those undergoing Furlow palatoplasty.
The risk for OSA appears to be higher after pharyngeal flap
compared to pharyngoplasty but studies in the area are limited by
lack of pre- and post-operative PSG data or because adult criteria
were used to define paediatric OSA. For example, in a retrospective
review of 52 patients the rate of obstructive symptoms during sleep
did not differ between those in the pharyngeal flap and pharyngoplastygroups (3 vs2 patients).80 Based onan RDI > 20 events/h,
OSA was present in the entire pharyngeal flap group with OSA
symptoms and none of thosewho underwent pharyngoplasty. Using
appropriate paediatric criteria, the Velopharyngeal insufficiency
(VPI) Surgical Trial Group78 concluded that the rate of OSA after
pharyngeal flap was similartothatof pharyngoplasty.However,only
half of the subjects underwent PSG pre- or post-operatively and it is
unclear how selection for PSG was made. OSA (OAHI > 1 event/h)
was not identified pre-operatively in any subjects in the pharyngeal
flap group while 10% of the pharyngoplasty group had OSA preoperatively. Twelve months after surgery, 21% of those with
pharyngeal flap had OSA (OAHI > 1 event/h) compared to 6.3% of
those with pharyngoplasty.
Overall, surgical procedures used to correct velo-pharyngeal
insufficiency confer a higher risk of OSA than primary palatoplasty. Factors that contribute to velo-pharyngeal insufficiency
such as poor palate function may compound the effect of significant limitation in nasal airflow after surgery. There is insufficient
information available to support a difference in risk of OSA with
variation in surgical techniques for either palatolplasty or
pharyngoplasty.


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Treatment of SDB
Information regarding treatment outcomes for SDB in association with CL/P is limited to retrospective reviews, case series and
case reports. The majority of studies focus on infants with Pierre
Robin sequence. Treatment options considered for infants and
children with isolated CL/P include tonsillectomy adenoidectomy (complete or partial), non-invasive ventilation (continuous
positive airway pressure; CPAP or bi-level positive airway pressure; BiPAP), septoplasty, maxillary distraction and reversal or
modification of surgical procedures which resulted in OSA.
Treatments reported in infants with Pierre Robin sequence include
prone sleep positioning (infants only), nasopharyngeal tubes,
nasal mask CPAP, tongue–lip adhesion, release of musculature of
the mouth floor, and mandibular distraction with tracheostomy
used as a last resort.
Treatment approaches for airway obstruction in Pierre Robin
sequence focus on the newborn or period of infancy. Airway
interventions in Pierre Robin sequence are reported to improve
feeding as well as breathing and sleep. Early airway intervention is
associated with improved growth and a reduced need for assisted
feeding.82 It is associated with earlier discharge from hospital, and
reduction in parental stress. A summary of the case series of airway
management in infants with Pierre Robin sequence is presented in
Table 4. Casouette-Laberge and colleagues83 report on 125 infants
who presented over the period of 1964 to 1991. They describe an
increase in the use of routine monitoring for signs of airway
obstruction including PSG in the later half of their study period
with a trend to a reduced mortality as well as earlier identification
of problems in ventilation. A more recent case series by Meyer and
colleagues84 examined cases between 1989 and 2006 and found an
increased use of surgical intervention in the later years. The
authors attributed this change to an increase in the use of
mandibular distraction for airway management of infants.
Prone positioning for sleep is reported to successfully relieve
airway obstruction for 40–60% of infants with Pierre Robin
sequence. A retrospective chart review over a 15 year period from
a single institution identified 40 children with Pierre Robin
sequence who were referred for airway management.85 Sixty-three
percent of children were successfully managed with prone positioning. In infants who survived the neonatal period, failure to
thrive despite prone positioning was linked to persistent airway
obstruction. Two large case series report successful management of
airway obstruction with prone positioning alone in 45% and 49% of
infants respectively.83,84

Table 4

Treatment of airway obstruction in infants with Pierre Robin sequence.
Reference N Treatment options Frequency
Meyer et al.84 74 No airway intervention or prone positioning 49%
Nasopharyngeal tube or short term intubation 19%
Surgical intervention: 32%
Mandibular distraction 24%
Tracheostomy 1%
Tracheostomy followed by distraction 7%
de Buys et al.110 48 No airway intervention 73%
CPAP 6%
Nasopharyngeal tube 21%
Alone 4%
With CPAP 17%
Li et al.24 110 Prone positioning 75%
Nasopharyngeal tube 2%
Endotracheal intubation 15%
Endotracheal intubation then: 8%
Tongue–lip adhesion 3%
Tongue–lip adhesion then tracheostomy 3%
Tracheostomy 2%
Caouette-Laberg
et al.83
125 Prone positioning þ bottle feeding 45%
Prone positioning þ gavage feeding 32%
Endotracheal intubation þ gavage feeding 23%
Pasyayan et al.111 25 Prone positioning 40%
Prone positing þ gavage feeding 48%
Nasopharyngeal tube 4%
Endotracheal tube 8%
Heaf et al.85,a 40 Prone positioning 63%
a Airway management of remaining infants is not described.

350 J.E. MacLean et al. / Sleep Medicine Reviews 13 (2009) 345–354

Nasopharyngeal airways can be used to physically stent the
airway to relieve airway obstruction that is present during
wakefulness and sleep. Heaf and colleagues85 reported on 12
infants with Pierre Robin sequence for whom nasopharyngeal
airway was used after failure of prone positioning. The mean
duration of use was 9.5 weeks. All infants without co-morbid
lower airway disease showed improvement in signs of airway
obstruction after placement of the nasopharyngeal airway.
Weight velocity improved with the use of nasopharyngeal airway
compared to infants for whom prone positioning failed to relieve
airway obstruction. Complications of nasopharyngeal airway use
included vomiting with incorrect positioning and mild nasal
excoriation. In another group of infants, nasopharyngeal airway
successfully managed airway obstruction in 40% of infants who
failed management with prone positioning alone.84 Nasopharyngeal airway is also reported to allow home care by parents for
select infants with airway obstruction.86,87 In a study of 13
infants referred for specialist airway management, 12 parents
were successfully trained in home use of nasopharyngeal tubes.
This resulted in a 60% reduction in the length of hospital stay
with comparable weight gain, and no complications or
readmissions.86

Nasal-continuous positive airway pressure (nCPAP) is an effective alternative method of treatment for OSA for both infants and
children with CL/P, including those with Pierre Robin sequence, and
is likely under-utilized. Infants who can maintain airway function
for feeding when awake may continue to need airway support
during sleep.58 In addition, older children with OSA occurring or
persisting after surgical procedures can be successfully managed
with nCPAP.88,89 The need for nCPAP and pressure requirements
should be reassessed as children grow to assess improvement or
resolution of OSA.88,90 It should also be noted that case reports
show an association between the use of nCPAP and maxillary
hypoplasia that has been ascribed to the pressure effect of the nasal
mask on the growing midface.91,92 Case series of the use of nCPAP in
children, however, have failed to identify this complication.93,94 The
potential effect of nCPAP on facial structures does appear to be
reversible with mask modification.91
Endoscopic adenoidectomy or partial adenoidectomy can
relieve upper airway obstruction in children with CL/P.95,96
However, this surgery carries risk for post-operative velo-pharyngeal insufficiency97 so the decision to use adenoidectomy to treat

OSA in children with CL/P should be made in consultation with
speech pathologists and surgeons experienced in the area.98
Procedures to bring the tongue forward, such as tongue–lip
adhesion, have been used for airway management in infants with
Pierre Robin sequence. This improves airway obstruction and
facilitates discharge from hospital60 but is associated with a variable rate of suture breakdown and the necessity for other airway
intervention.24,99 Freed and colleagues100 demonstrated improvement on PSG after tongue–lip adhesion in four infants. Improvements were sustained after palatoplasty and take down of the
tongue–lip adhesion. An alternative approach is the use of oral
appliances. A study of an appliance with a velar extension
demonstrated successful treatment in 11 patients with Pierre Robin
Sequence.101

The correction of septal deviation can be used to treat OSA in
a sub-set of children with CL/P. Septopalatal protraction is nonsurgical and may also be feasible in infants.102 Josephson and
colleagues61 report successful surgical management of OSA in 2
children after cleft lip repair conservative septoplasty before one
year of age. Other surgical options include maxillary distraction
osteogenesis, which has been reported in older children with
a history of CL/P,103 as well as Le Fort I osteotomy with maxillary
advancement.104,105
Additional surgical options include modification or reversal of
the original procedure and may be required if OSA occurs after
surgery, including surgical correction of velo-pharyngeal insufficiency.106,107 Lesavoy and colleagues73 reported that perioperative
airway obstruction warranted flap reversal in 10% of their
patients. A case report of an 8-year-old female describes OSA
following mid-line flap pharyngoplasty at 5 years of age.106 She
developed loud snoring and poor growth necessitating revision of
the pharyngoplasty, but she proceeded to complete reversal of
the procedure before her OSA resolved. One author suggests that
any child who has large tonsils and undergoes pharyngoplasty
should have the tonsils removed at the time of the
pharyngoplasty.108

Mandibular distraction osteogenesis is an option to improve
airway size and patency. This procedure is an option for a select
group of neonates, especially those with Pierre Robin sequence and
severe OSA. In general, this group of infants has airway obstruction
when awake and asleep as well as failure to thrive. The procedure
involves placement of a distraction device with pins placed on each
mandibular ramus after corticotomy. Mandibular distraction is then
completed over a period of time with daily manual distraction until
the desired distraction length is reached. Denny et al.109 describe
outcomes of this procedure in a series of neonates with Pierre Robin
sequence who would have otherwise required tracheostomy for
ventilation by consensus of the medical and surgical teams. Over
a 22-month period, 5 of 6 infants successfully avoided tracheostomy through the use of mandibular distraction while the last
infant had multiple airway lesions and underwent tracheostomy.
Distraction distances of 8–15 mm were achieved by advance of
1–2 mm per day with treatment completed by 6 weeks in all cases.
With follow-up ranging from 9 to 22 months, all infants who
underwent distraction avoided tracheostomy, met or exceeded
target weight gains and demonstrated relief of airway obstruction
on bronchoscopy. In another retrospective case series from a single
clinic, 18 of 24 infants who failed medical management of airway
obstruction underwent mandibular distraction, with an additional
5 patients undergoing distraction following tracheostomy.84
The largest study describing treatment of OSA in children with
CL/P is a retrospective review which identified symptoms of OSA in
120 children (66 children with isolated CL/P, 54 children with CL/P
in the context of a syndrome).55 Children with syndromes were
more likely to have been recommended for PSG (84% with
syndromes vs 55% isolated), were less likely to be recommended for
surgery without a PSG (8% with syndromes vs 21% isolated) and
were less likely to undergo observation only (7% with syndromes vs
23% isolated). All but one child who underwent PSG had an RDI > 1.
Of children who underwent PSG, 58% had surgical intervention; the
majority had tonsillectomy and partial adenoidectomy (38%) or
tonsillectomy alone (23%). Children with syndromes were also
more likely to be recommended for surgery (71% vs 37%). Of 25
children who had PSG before and after surgery, OSA resolved in
only 12% of children, improved in 28%, was unchanged in 32% and
was worse in the remaining 28%. The authors do not report the
outcome of 28 patients who had abnormal PSG and did not undergo
surgery. In the second retrospective review,56 the authors reported
follow-up PSG results for 21 of 62 patients (34%). Of these 21
patients, 9 (43%) had non-invasive respiratory support recommended between the 1st and 2nd PSG including BiPAP in 1 patient.
Five children underwent surgery, with tonsillectomy adenoidectomy for 2 patients and palatoplasty for 3 patients. Two patients
underwent observation only. Follow-up PSG showed improvement
for 6 children (29%), no change for 4 children (19%) and worsening
in 11 (52%).
A range of treatment options are available for infants and children with SDB and CL/P. The majority of infants with Pierre Robin
J.E. MacLean et al. / Sleep Medicine Reviews 13 (2009) 345–354 351
sequence are reported to be successfully managed with prone
positioning and/or nasopharyngeal tubes while a minority will
require surgical intervention. Children with CL/P can be treated
with adenotonsillectomy but removal of the adenoid tissue carries
a risk of velo-pharyngeal insufficiency. Other treatment options for
both infants and children with SDB and CL/P include CPAP and
surgery to augment the upper airway space.

Outstanding issues

The longitudinal history of SDB in association with CL/P is
unknown. A case study reports a dramatic fall off in growth
following pharyngoplasty with catch up following complete
reversal of the procedure.107 One study reports more severe OSA in
children with cleft palate following pharyngeal flap compared to
the same procedure in adults.70 It is not known whether SDB in
infancy, such as seen in infants with Pierre Robin sequence, carries
a greater effect on cognition because of the effects of intermittent
hypoxia on a brain in the early stages of development or a lesser
effect because of brain protective mechanisms in early development. Children with CL/P do show cognitive differences from nonCL/P children across a range of ages19,20 and SDB may contribute to
this difference.
Little is known about the spectrum of SDB other than OSA which
is the predominant type of SDB studied. Snoring is mentioned in
several papers but the proportion of children with CL/P who snore
is unknown. Several papers also describe the occurrence of central
apnoeas either concurrent with obstructive apnoeas, after resolution of obstructive apnoeas or in isolation.55,59,63,68,69,72 It is unclear
whether this represents a secondary phenomenon because of longterm exposure to intermittent hypoxia associated with OSA, or
a primary difference in the mechanisms of respiratory control in
children with CL/P.
The issue of reducing surgical risks also requires further investigation. Surgery is the mainstay of treatment for CL/P to normalize
appearance and to improve function with a focus on feeding and
speech. Multi-centred studies are needed to understand the
contribution of the type of surgery and surgical procedure on the
risk of SDB. This should include investigation of the effect of surgery
on upper airway muscle function pre- and post-operatively to
understand how airway anatomy and function contribute to the
occurrence of OSA in children with CL/P.
There have been no studies published to date which have
investigated the relative success rates of the various treatment
options for SDB in children with CL/P, except for those pertaining to
infants with Pierre Robin sequence. More information is needed on
the outcomes of both surgical and non-surgical treatment modalities for SDB in children with CL/P.

Conclusion

Dysfunction of the palatal muscles controlling the soft palate in conjunction with structural abnormalities of the maxilla and
mandible producing a small nasopharyngeal airway underlie the high risk for SDB in children with CL/P. The risk is compounded by surgical procedures to correct the structural abnormalities which further reduce airway dimensions. Until further information about specific risk factors is obtained, children with a CL/P, regardless of surgical status, should be screened for SDB. Treatment options need to be balanced against risks, particularly deterioration in speech function after adenoidectomy, or persisting SDB because of the abnormal function and anatomy of their palate and airway.
Further research into the short- and long-term outcomes of SDB in CL/P is required to enable clinicians to make appropriate treatment decisions for children with CL/P.


Practice points

Children with CL/P should be screened for symptoms of
SDB.
A low threshold should be set for completing PSG for
the investigation of SDB in children with CL/P.
While standard therapy for SDB may be appropriate for
children with CL/P, the decision to remove adenoid
tissue should be done in consultation with those experienced in the care of children with CL/P.
Follow-up of children with CL/P is required after treatment to determine the success of surgical procedures
and to identify residual SDB.


Research agenda
Prospective longitudinal studies of infants and children
with CL/P are needed to determine the risk, important
risk factors and outcome for SDB associated with CL/P.
Treatment studies of children with SDB should include
children with a history of CL/P to determine the relative
contribution of facial structure to the success of treatment modalities for SDB.


* The most important references are denoted by an asterisk.

352 J.E. MacLean et al. / Sleep Medicine Reviews 13 (2009) 345–354

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354 J.E. MacLean et al. / Sleep Medicine Reviews 13 (2009) 345–354

Groet RuudJ
Groet RuudJ
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Re: Schisis & Apneu (Deel 2)

4
Hoi Menno,

en dit is slechts deel 2. Dan heb je deel 1 nog niet gezien. Ik heb de conclusies van het rapport uit 2009 in Deel 1 aan het begin gezet in Blauw en in het Rood. De rest hoef je dan niet te lezen. Maar ik wilde het rapport toch even veilig bewaren voordat het in mijn administratie verdwijnt.

Groet RuudJ

Ps. Het is ook moeilijk te lezen met al die medische termen en dan ook nog in het Engels wat voor de meeste van ons niet onze moedertaal zal zijn.
Groet RuudJ
Medewerker AV-Kenniscentrum
ADEM BEWUST, WANT HET LEVEN DUURT MAAR KORT.
Bent u al lid van onze Apneuvereniging? €32,50 / Incasso €30,00/Jaar
Word lid en ontvang 4X het Apneu Magazine + 10X het Apneu bulletin per jaar